Tuberous sclerosis complex (TSC) regulates cell growth in response to energy stress by inhibiting the master kinase mechanistic target of rapamycin complex (mTORC1). TSC hydrolyzes RAS homolog-mTORC1 binding (RHEB) from its GTP-bound to GDP-bound state, thereby preventing the allosteric activation of mTORC1. Loss-of-function mutations in TSC hyperactivate mTORC1, leading to the common genetic disorder TSC, characterized by excess cell growth and tumor formation. Here, we overcome a high degree of continuous conformational heterogeneity to determine the 2.8 Å cryo-electron microscopy (cryo-EM) structure of the complete human TSC in complex with the lysosomal recruitment factor WIPI3. TSC forms an elongated 40 nm wing-like structure with a core HEAT-repeat scaffold formed by a TSC2 dimer, centrally joined by two juxtaposition catalytic domains. The TSC1 coil-coil dimer runs across the TSC2 surface, forming a previously undetected N-terminal TSC1 dimer that clamps onto the core scaffold on a single TSC wing. Structural and biochemical analysis reveal a novel phosphatidylinositol phosphate (PIP)-binding pocket in the TSC1 dimer interface, which specifically binds singularly phosphorylated PIPs. WD repeat domain phosphoinositide-interacting-protein-3 (WIPI3) binds to the extreme tip of the complex through a conserved motif in TSC1, providing a second membrane anchor point for TSC lysosomal recruitment. These structural advances help explain how TSC and WIPI3 coordinate with endolysosomal PIP-signaling networks to regulate mTORC1 activity at the lysosome. Furthermore, the high-resolution structure of the complete human TSC the identification of novel mutational hotspots and uncover new mechanisms of TSC dysregulation in disease.